Poster presentation

The class of immune response against autoantigens could profoundly influence the onset
and/or outcome of autoimmune diseases. Until now, there is only limited information
on the antigen-specific balance between proinflammatory and regulatory responses in
humans. Here we analyzed the natural immune response against a candidate autoantigen
in rheumatoid arthritis, Human Cartilage gp-39 (HC gp-39).

Peripheral blood mononuclear cells from healthy individuals reacted against HC gp-39
with the production of IL-10, but not interferon gamma (Fig. 1). Ex vivo assays indicated that the naturally occurring HC gp-39-specific immune response in
bulk is powerful enough to suppress antigen-specific recall responses, demonstrating
that, rather than being unresponsive, the HC gp-39-directed immune response in healthy
individuals shows a strong bias towards a regulatory phenotype. Moreover, CD4+ T-cell lines directed against HC gp-39 expressed CD25, GITR and Foxp3 molecules and
were capable of suppressing antigen-specific T-cell responses. Cell–cell contact was
required for this suppression. As opposed to healthy individuals, the HC gp-39-directed
immune response in 50% of patients with rheumatoid arthritis exhibits polarization
towards a proinflammatory Th1 phenotype and is significantly less powerful in suppressing
antigen-specific recall responses.

Together these findings indicate that the presence of HC gp-39-specific immune responses
in healthy individuals may have an inhibitory effect on inflammatory responses in
areas where HC gp-39 is present. Furthermore, these data indicate that the class of
HC gp-39-directed immune response in RA patients has shifted from an anti-inflammatory
towards a proinflammatory phenotype.

Acknowledgements

This work was supported by The Dutch Arthritis Association. REMT is supported by a
Vidi Grant from the Netherlands Organization for Scientific Research. HvD and LRL
are supported by The Netherlands Organization for Health Research and Development.